The objective of this research proposal is to investigate the contribution of a reticuloendothelial depressing substance to the reticuloendothelial system (RES) depression during clinical and experimental shock states. The RES functions as an important host defense mechanism during shock and the failure of this system may be important in the pathogenesis of irreversible shock. RE depressing substance was first described by Blattberg and Levy as a low molecular weight peptide which is capable of depressing RES phagocytic function and increasing the susceptibiltiy to experimental shock. Preliminary data presented in this proposal verifies the presence of RE depressing substance in the circulation of shock animals. The presence of RE depressing substance in clinical and experimental shock states will be related to the degree of RES depression during experimental shock. The mechanism of action of this substance will be studied in terms of effects on factors that may contribute to the RES depression during shock, i.e. hepatic blood flow, hepatic Kupffer cell function and circulating activity of opsonic protein (alpha-2-glycoprotein). It will also be possible to evaluate the effectiveness of the administraton of purified opsonic protein as a potential means of reversing the effects of RE depressing substance. Additionally, the similarities between RE depressing substance and myocardial depressing factor will be studied.